This invention relates to a series of novel chemotherapeutic agents and a process for the preparation thereof; in particular, it relates to 1,3 (2H,4H)-dioxoisoquinoline-4-carboxamides.
The prior art teaches that primary and secondary carboxamide groups can be substituted for an active hydrogen atom by reacting isocyanic acid or appropriate isocyanate with an organic molecule containing the active hydrogen.
However, this process is not suitable for the preparation of tertiary carboxamides. For this reason, it was desired that 1,3 (2H,4H)-dioxoisoquinoline-4-carbalkoxy compounds be prepared, since aminolysis of the esters with appropriate secondary amine would provide a facile synthesis of tertiary carboxamides of the instant invention. Unexpectedly, treating homophthalimide with ethyl chloroformate under basic conditions, usually a satisfactory procedure for generating a carbethoxy derivative, resulted in an unsatisfactory yield of the desired product.
The prior art also teaches that treating an amide with alcohol is usually a poor method of preparing the corresponding ester. One skilled in the art would expect the interconversion between ester and carboxamide to favor the formation of the carboxamide at the expense of the ester.